The cardenolide UNBS1450 is able to deactivate nuclear factor κB–mediated cytoprotective effects in human non–small cell lung cancer cells

Mijatovic, Tatjana; Beeck, Anne Op De; Quaquebeke, Eric Van; Dewelle, Janique; Darro, Francis; Launoit, Yvan de; Kiss, Róbert

doi:10.1158/1535-7163.mct-05-0367

Cited by 103 publications

(64 citation statements)

References 48 publications

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“…The overall growth levels of the human cancer cell lines were determined using the colorimetric MTT [3-(4,5-dimethylthiazol-2yl)]-diphenyltetrazolium bromide, Sigma, Belgium) assay (12)(13)(14)(15)(16)(17). Briefly, cell lines were incubated for 24 h in 96-microwell plates at concentrations of 10,000-40,000 cells/ml, depending on the cell type, to ensure adequate plating prior to making cell growth determinations.…”

Section: Methodsmentioning

confidence: 99%

“…The number of living cells after 72 h of culture in the presence (or absence for the negative control) of the various compounds was directly proportional to the intensity of the blue colour, which was measured quantitatively by spectrophotometry using a Bio-Rad Model 680XR (Bio-Rad, Nazareth, Belgium) at the 570-nm wavelength (with a reference wavelength of 630 nm). Each experimental condition was run six times (12)(13)(14)(15)(16)(17). Quercetin was obtained from Sigma (Bornem, Belgium), and quercetin-3-O-glucuronide (miquelianin) and quercetin-3-Ogalactoside (hyperoside) were obtained from Carbosynth (Compton, Berkshire, England).…”

Section: Methodsmentioning

confidence: 99%

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Quercetin inhibits a large panel of kinases implicated in cancer cell biology

Kiss

2011

Int J Oncol

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Abstract. Flavonoids are polyphenolic secondary metabolites from plants that possess a common phenylbenzopyrone structure (C6-C3-C6). Depending upon variations in their heterocyclic C-ring, flavonoids are categorised into one of the following groups: flavones, flavonols, flavanones, flavanols, anthocyanidins, isoflavones or chalcones. Flavonols include, among others, the molecules quercetin, myricetin and kaempferol. The anticancer activity of flavonols was first attributed to their electron-donating ability, which comes from the presence of phenolic hydroxyl groups. However, an emerging view is that flavonoids, including quercetin, may also exert modulatory actions in cells by acting through the protein kinase and lipid kinase signalling pathways. Data from the current study showed that 2 μM quercetin, a low concentration that represents less than 10% of its IC 50 growthinhibitory concentration as calculated from the average of eight distinct cancer cell lines, decreased the activity of 16 kinases by more than 80%, including ABL1, Aurora-A, -B, -C, CLK1, FLT3, JAK3, MET, NEK4, NEK9, PAK3, PIM1, RET, FGF-R2, PDGF-R· and -Rß. Many of these kinases are involved in the control of mitotic processes. Quantitative video microscopy analyses revealed that quercetin displayed strong anti-mitotic activity, leading to cell death. In conclusion, quercetin partly exerts its anticancer activity through the inhibition of the activity of a large set of kinases. Quercetin could be an interesting chemical scaffold from which to generate novel derivatives possessing various types of antikinase activities.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Quercetin inhibits a large panel of kinases implicated in cancer cell biology

Kiss

2011

Int J Oncol

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“…A growing number of reports document the ability of some CS to circumvent cancer cell chemoresistance [50][51][52][53][54], making them an interesting starting point for the development of new anti-chemoresistance treatment strategies.…”

Section: Cardiotonic Steroidsmentioning

confidence: 99%

“…Many tumour cells display constitutively high levels of nuclear NF-κB activity due to the hyperactivation of the NF-κB signalling pathways or to inactivating mutations in the regulatory Iκ-B subunits [76][77][78]. Several CS have already been shown to interfere with the NF-κB pathway [51,[79][80][81]. We previously reported that 19-hydroxy-2′′-oxovoruscharin (UNBS1450) is able to sensitise chemoresistant, highly aggressive, and naturally therapy-resistant A549 NSCLC cancer cells by deactivating the cytoprotective effects caused by constitutively activated NF-κB [51].…”

mentioning

confidence: 99%

“…Several CS have already been shown to interfere with the NF-κB pathway [51,[79][80][81]. We previously reported that 19-hydroxy-2′′-oxovoruscharin (UNBS1450) is able to sensitise chemoresistant, highly aggressive, and naturally therapy-resistant A549 NSCLC cancer cells by deactivating the cytoprotective effects caused by constitutively activated NF-κB [51]. This UNBS1450-induced deactivation of the NF-κB pathways occurs at several levels, including both the inhibitory I-κB portion of the NF-κB signalling pathway and its stimulatory p65/Rel-A NF-κB portion.…”

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confidence: 99%

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Untitled

2013

Planta Med

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Total Syntheses of Polyhydroxylated Steroids by an Unsaturation‐Functionalization Strategy

et al. 2023

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Highly oxygenated cardiotonic steroids, such as ouabain, possess a wide spectrum of biological functions and remain significant synthetic challenges. Herein, we have applied an unsaturation-functionalization strategy and developed a synthetic method in addressing the C19-hydroxylation issue for efficient synthesis of polyhydroxylated steroids. An effective asymmetric dearomative cyclization allowed the construction of the C19-hydroxy unsaturated steroidal skeleton in only four steps from the Hajos-Parrish ketone ketal 7. The synthetic sequence featured C3À OH-directed hydrogenation/epoxidation, m-CPBAtriggered epoxidation/S N 2' nucleophilic substitution, Birch reduction of an enone, and regioselective LiAlH 4 reduction to furnish the polyhydroxy functionalities on the steroid skeleton with high stereochemical control and efficiency. This approach ultimately enabled the total synthesis of 19-hydroxysarmentogenin and ouabagenin in 18 and 19 steps, respectively, overall. The synthesis of these polyhydroxylated steroids offers synthetic versatility and practicality in the search for new therapeutic agents.

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The cardenolide UNBS1450 is able to deactivate nuclear factor κB–mediated cytoprotective effects in human non–small cell lung cancer cells

Cited by 103 publications

References 48 publications

Quercetin inhibits a large panel of kinases implicated in cancer cell biology

Quercetin inhibits a large panel of kinases implicated in cancer cell biology

Untitled

Total Syntheses of Polyhydroxylated Steroids by an Unsaturation‐Functionalization Strategy

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